Magnetic resonance imaging (MRI) and positron emission tomography (PET) are widely used imaging technologies with both clinical and biomedical research applications. MRI's strengths include high resolution and high contrast morphologic imaging of soft tissues, the ability to image physiologic parameters (i.e. diffusion, perfusion) and the measurement of metabolites using chemical shift imaging. PET images the distribution of biologically-targeted radiotracers with high sensitivity, but images generally lack anatomic context and are of lower spatial resolution. There are clear synergies between the two modalities, as each can provide unique information not attainable with the other modality. To date, PET and MR images are acquired on separate imaging systems, and co registered using software approaches. However, acquiring PET and MRI data sequentially rules out the possibility of temporally correlating PET and MRI findings. Biological systems are inherently dynamic, and their response to drugs, contrast agents, and other external stimuli can also be strongly time-dependent. An MRI-compatible PET scanner has been built for brain applications that allow data from both modalities to be acquired simultaneously. This new technology will permit acquisition of temporally correlated data showing the distribution of PET radiotracers and MRI contrast agents or MR- detectable metabolites, with registration to the underlying anatomy. In this proposal we aim to advance this MR-PET instrumentation toward meaningful clinical human use by a series of steps whereby we will validate this technology, identify methods to best exploit the combined data, and apply these methods to patients with newly diagnosed glioblastoma (GBM). We particularly seek to focus on quantitation of the output of the system because many advanced applications will require fully quantitative data. Specifically, we will: (1) Assess and optimize the performance of the integrated system. We hypothesize the performance of the combined MR-PET scanner will be similar to that of the stand-alone instruments for a range of protocols currently in use for clinical and research applications. (2) Validate methods to improve the quantification of the PET data using the simultaneously acquired MR data. We hypothesize that the MR information can be used to perform PET attenuation and motion correction and to obtain an estimate of the arterial input function. (3) Use the combined system and the methods developed for performing quantitative MR-PET assessment of response to therapy in GBM patients. We hypothesize that parameters derived from the dynamic PET data analysis may provide additional information to static PET studies, and that this information may supplement the information provided by the MRI. PUBLIC HEALTH RELEVANCE: Combined magnetic resonance and positron emission tomography is a very promising technology for clinical and research applications. In this work we validate this new technology and explore its potential utility for the quantitative assessment of therapy response in glioma patients.